rs2235041

Variant names:

• chr7-87536418-G-A
• rs2235041
• NM_001348946.2:c.2481+40C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(ABCB1):​c.2481+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00534 in 1,595,404 control chromosomes in the GnomAD database, including 377 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (192 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (185 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 5 publications found

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.2481+40C>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.2691+40C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2481+40C>T		intron	N/A	NP_000918.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.2481+40C>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.2481+40C>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.2289+40C>T		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4047 AN: 152046 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00705 AC: 1770 AN: 251078 AF XY: 0.00500

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.00417

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00309 AC: 4460 AN: 1443240 Hom.: 185 Cov.: 28 AF XY: 0.00260 AC XY: 1868 AN XY: 719124

African (AFR) AF: 0.104 AC: 3438 AN: 33088

American (AMR) AF: 0.00515 AC: 230 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00211 AC: 55 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.000384 AC: 33 AN: 85878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00662 AC: 38 AN: 5744

European-Non Finnish (NFE) AF: 0.000249 AC: 273 AN: 1095126

Other (OTH) AF: 0.00658 AC: 393 AN: 59740

GnomAD4 genome AF: 0.0267 AC: 4063 AN: 152164 Hom.: 192 Cov.: 32 AF XY: 0.0255 AC XY: 1897 AN XY: 74392

African (AFR) AF: 0.0916 AC: 3801 AN: 41484

American (AMR) AF: 0.0114 AC: 174 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68012

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0111 Hom.: 79

Bravo AF: 0.0309

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.72
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2235041; hg19: chr7-87165734;